Since ESR1 fusion driven growth of ER-positive breast cancers remained sensitive to CDK4/6 inhibition, the presence of an ESR1-e6>fusion could be a putative biomarker to stratify patients for CDK4/6 inhibitor therapy after resistance to endocrine treatment or continued CDK4/6 inhibitor therapy with a second targeted therapy after resistance to first line treatment for metastatic disease with endocrine therapy in combination with a CDK4/6 inhibitor. The gene discussed is CDK4; the disease is metastatic neoplasm.